Development of challenging Pd0-catalyzed enantioselective C(sp3)-H activation reactions

Research Project
|
01.04.2019
- 31.03.2023

This proposal focuses on the development of challenging enantioselective C-H activation reactions that proceed by palladium(0)-catalysis. It builds on previous research from our group in this field and on the analysis of current gaps and challenges. The proposal is divided into four independent Work Packages (WP), wherein different types of chiral catalysts will be employed. WP1 is dedicated to the development of an enantioselective method to synthesize axially chiral spirocycles, involving a double C(sp3)-H arylation and the desymmetrization of enantiotopic methyl groups in the enantiodetermining step. This method should provide a straightforward access to original spirocyclic molecules wherein the stereogenic axis is the sole stereogenic element. In WP2, we will investigate the yet unexplored kinetic resolution of racemic reactants by Pd0-catalyzed activation of sp2 and sp3 C-H bonds in the presence of a chiral catalyst. Ideally, both enantiomers of the corresponding cyclic products could be formed by reacting the remaining enantiomer in the presence of an achiral catalyst. Applications to the synthesis of polycyclic natural products are envisaged for selected cases. The main purpose of WP3, for which we already have very significant preliminary results, is the Pd0-catalyzed functionalization of enantiotopic secondary C-H bonds. These are less reactive than primary ones and more challenging to activate, but lead to the creation of a stereocenter at the activated site and have a great application potential. The use of C2-symmetric N-heterocyclic carbenes of the IBiox family should allow achieving high enantioselectivities for a range of synthetically appealing carbo- and heterocyclic products. The developed methods will be applied to the synthesis of selected natural products such as indidene C. WP4 is dedicated to the development of the intermolecular enantioselective C-H functionalization of enantiotopic secondary C-H bonds. The use of palladium(0) instead of the more established palladium(II) catalysis would enable cross-couplings with a variety of compatible electrophiles. Reactions of substrates bearing simple monodentate directing groups, potentially leading to a range of valuable enantioenriched carboxylic acid, amine or alcohol building blocks in a straightforward manner, will be investigated.

Funding

Development of challenging Pd0-catalyzed enantioselective C(sp3)H activation reactions

SNF Projekt (GrantsTool), 04.2019-03.2023 (48)

PI : Baudoin, Olivier.

Members (1)

Olivier Baudoin

Principal Investigator

Research Groups

Organometallic Catalysis for Organic Synthesis